International Journal of Pharmacology and Clinical Sciences, 2015, 4, 2, 12-15.
DOI: 10.5530/ijpcs.4.2.1
Published: June 2015
Type: Original Article
Authors: Surendiran A, Pradhan SC, Subrahmanyam DKS, Aparna Agrawal, Umamaheswaran G, Rajan S, and Adithan C
Author(s) affiliations:
Surendiran A1*, Pradhan SC1, Subrahmanyam DKS2, Aparna Agrawal2, Umamaheswaran G1, Rajan S1, Adithan C3
1Department of Pharmacology, JIPMER, Puducherry, India.
2Department of Medicine, JIPMER, Puducherry, India.
3Department of Clinical Pharmacology, JIPMER, Puducherry, India.
Abstract
Background: Glibenclamide is a substrate and an inhibitor of P-glycoprotein which is coded by the gene ABCB1. Objective: To study the influence of ABCB1 C3435T gene polymorphism on the therapeutic effect of glibenclamide, its plasma levels and hypoglycemic adverse effects. Materials and Methods: The study was done in Type 2 diabetes mellitus patients of South India (n=80) who were on treatment with glibenclamide as a single agent or along with metformin. From a venous blood sample, ABCB1 C3435T genetic polymorphism and plasma levels of glibenclamide were determined. The parameters were compared between genotype groups. Patient characteristics across genotypes were analyzed using one-way ANOVA and the association between glycemic status and genotype was studied using Chi Square test. The association between genotypes and parameters such as C/D values, hypoglycemic episodes were compared using Kruskal Wallis Test. Results: There were no significant differences in age, body mass index, and duration of treatment between the genotype groups ABCB1 CC, CT, and TT. There was no significant association between glycemic status of type 2 diabetes and presence of variant genotypes ABCB1 CT and TT. There were no statistically significant differences in plasma concentration of glibenclamide, number and severity of adverse effects between the genotype groups. Conclusion: ABCB1 C3435T genetic polymorphism did not produce any significant influence on the therapeutic response to glibenclamide, plasma glibenclamide levels and the occurrence of adverse events in South Indian patients with type 2 diabetes mellitus.
Keywords: ABCB1 C3435T, Diabetes Mellitus, Drug Transporters, Glibenclamide, MDR1, Personalized Medicine, Pharmacogenetics